The eye is a complex and sensitive organ of the body, which can experience numerous diseases. The eye poses many barriers to protect any damage to its tissues. This also means that the anterior portion of the eye is more susceptible to diseases. The first and foremost barrier is the conjunctiva, which is the mucous membrane surrounding the eye ball. It is constantly exposed to many harsh conditions/allergens through the environmental factors it encounters. This leads to the allergic reactions in the eye mediated by mast cells through the release of histamine leading to the condition called allergic conjunctivitis or other associated inflammatory conditions like redness and swelling of the eye. These allergic conditions are either seasonal which occurs only during specific time of the year and is termed seasonal allergic conjunctivitis (SAC) or perennial that occurs throughout the year and termed perennial allergic conjunctivitis (PAC). Some allergic conditions extend even to the cornea such as atopic keratoconjunctivitis, vernal conjunctivitis and giant papillary conjunctivitis.
These conditions are typically characterized by red, itchy and swollen eyes with watery discharge. This is largely attributed to the degranulation of mast cells due to the cross-linking of IgE upon allergen sensitization leading to an outburst of histamine in the conjunctiva. The conjunctiva being rich in mast cells, experiences an overdose of histamine upon allergen sensitization, resulting in the itching and redness of the eye. Current treatment methods involve anti-histamine drops (emedastine difumarate and levocabastine), topical mast cell stabilizers (olopatadine, ketotifen), decongestants and topical anti-inflammatory drugs (NSAID's and corticosteroids).
Allergic rhinitis is an inflammation of the nasal passages, usually associated with watery nasal discharge and itching of the nose and eyes. The symptoms occur in the nose and eyes and usually occur after exposure to dust, danders, or certain seasonal pollens. Patients can be severely restricted in their daily activities, resulting in excessive time away from school or work. Millions of dollars are spent each year on physician services and medication for treatment of this chronic illness. Many perennial and seasonal allergens cause allergic rhinitis the former giving rise to perennial allergic rhinitis (PAR) and the latter giving rise to seasonal allergic conjunctivitis (SAR).
Dust mites, cockroaches, molds and animal dander, are examples of year-around allergens.
Characteristic symptoms include repetitive sneezing; rhinorrhea (runny nose); post-nasal drip; nasal congestion; pruritic (itchy) eyes, ears, nose or throat; and generalized fatigue. Symptoms can also include wheezing, eye tearing, sore throat, and impaired smell. A chronic cough may be secondary to postnasal drip, but should not be mistaken for asthma. Sinus headaches and ear plugging are also common.
Anti-Histamines and Decongestants for Allergic Conjunctivitis
Anti-histamines are available for treating Allergic Conjunctivitis and are available in the market as tablets, capsules and liquids, and may or may not be combined with decongestants. Common anti-histamines include brompheniramine or chlorpheniramine, and clemastine. Non-sedating (less likely to cause drowsiness) long-acting anti-histamines include loratidine and fexofenadine. Oral decongestants alone may be helpful, including pseudoephedrine.
Nasal Sprays
For rhinorrhea, a nasal spray of cromolyn sodium (Nasalcrom) or a steroid nasal spray, such as flunisolide (Nasalide), beclomethasone dipropionate (Beconase, Vancenase), triamcinolone acetonide (Nasacort), and fluticasone (Flonase), may work so well that additional anti-histamines or decongestants are unnecessary. It is important to remember that improvement may not occur for one to two weeks after starting therapy with steroid nasal sprays. Short courses of oral corticosteroids may usually be indicated when severe nasal symptoms prevent the adequate delivery of topical agents. But due to their unpleasant side-effects, there has been a tremendous surge in demand for non-steroidal, plant based anti-inflammatory and anti-allergic agents and their potential use in various therapeutic applications. Curcuminoids are one such class of compounds that have proven anti-inflammatory and anti-allergic properties.
Curcuminoids are natural, polyphenolic compounds present in turmeric in three different forms a) Curcumin b) Bisdemethoxy curcumin and c) Demethoxy curcumin. Curcumin is the principal curcuminoid and has exceptionally potent antioxidant and anti-inflammatory activity, which can prevent cell damage caused by free-radicals (oxidative stress) and inflammation. The current level of interest on curcumin and its analogs/derivatives is known from the below mentioned articles.
Process for producing enriched fractions of bis-o-demethylcurcumin and tetrahydrotetrahydroxy-curcumin from the extracts of curcuma longa is disclosed in our earlier PCT Application #WO/2007/043058. According to this publication, bis-o-demethyl curcumin shows most potent anticancer, anti-oxidative and anti-inflammatory activity when compared to other curcuminoids and the natural mixture of curcumins.
However, the use of natural curcuminoids, such as curcumin, bisdemethoxycurcumin demethoxycurcumin and synthetically derived bis-o-demethyl curcumin and/or other demethylated curcuminoids either alone or in combination in ophthalmic formulations is not known in the prior art. Natural curcuminoids, such as curcumin, bisdemethoxycurcumin demethoxycurcumin and synthetically derived bis-o-demethyl curcumin and/or other demethylated curcuminoids either alone or in combination being a lipophilic drug have low aqueous solubility, and hence restrict the therapeutic availability of the same.
All curcuminoids, both natural and synthetic have lipophilic structures with conjugated double bonds with a keto group thus rendering them to have a dielectric constant which will interact with negatively charged membranes making it unable to permeate through the biological membrane. Thus, for these curcuminoids to pass through membranes, it is necessary to encapsulate these molecules with lipophilic molecules. Moreover, it is necessary to make the lattice of molecules as a single entity so that these encapsulated molecules can be transported across membranes.
Anti-allergic and anti-inflammatory drugs are classified into analgesics, anti-histamines, anti-microbials, corticosteroids and non steroidal anti-inflammatory drugs (NSAIDs). These classes of drugs are used to treat variety of ocular disorders. Prolonged use of corticosteroids, NSAIDs, and the other groups of above mentioned classes of drugs results in glaucoma, optic nerve damage, vision problems, cataract, or secondary ocular infections.
Accordingly, the current disclosure provides a potential successor in the field of ophthalmology with a novel phytopharmaceutical composition for the treatment of ocular and nasal diseases/disorders. Surprisingly, preliminary experiments conducted have demonstrated the use of surfactants and cosolvents in solubilizing curcuminoids up to 200 mg w/v thereby aiding effective solubilization in aqueous medium. The current method involves coating of curcuminoids using surfactants and a cosolvent in order to enhance the curcuminoids aqueous solubility and hence its permeation across the cell membrane.
Therefore, the current disclosure describes hitherto unexploited and novel ophthalmic composition(s) comprising natural curcuminoids, such as curcumin, bisdemethoxycurcumin demethoxycurcumin and synthetically derived bis-o-demethyl curcumin and/or other demethylated curcuminoids either alone or in combination, together with surfactants and/or cosolvents as aqueous ophthalmic composition(s) in the form of gel/suspension/ointment for ocular diseases or disorders.